Plasma exchange in highly sensitized patients as induction therapy after renal transplantation.
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Biomedical subjects
Publications and source records attributed to A Hartmann.
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We determined the pattern of mutations in exons 2-11 and adjacent intronic regions in breast cancers from Midwestern US white women. Twenty-one mutations were detected in 53 tumors (39.6%). Comparisons of the pattern of mutations within exons 5-9 showed that the frequency of missense mutations (44%) was lower in breast cancers of US Midwestern women than in most tumor types including breast cancers in other populations. Compared to breast cancers reported in a Scottish population, US women had a high frequency of G:C-->T:A transversions (P = 0.046). These findings suggest that environmental or endogenous factors contribute to p53 mutagenesis in mammary tissue to different extents among different populations. With a median follow-up of 19 months, the presence of a mutation was associated with shorter time to disease recurrence (P = 0.05) and shorter survival (P = 0.003). Putative dominant negative missense-type mutations (missense and in-frame microdeletions; P = 0.001) and null mutations (hemizygous nonsense and frameshift mutations; P = 0.007) were equally ominous. Thus, tumors with missense p53 mutations resulting in over-expression of a dysfunctional but otherwise intact protein have a clinical outcome similar to tumors with null mutations resulting in a truncated or garbled protein.
Sympathetic reinnervation was evaluated in 15 patients 2-69 months after heart transplantation using a double-tracer technique with 123I-MIBG and 201Tl. Since MIBG is accumulated in the same manner as norepinephrine it may serve as a tracer of the integrity and function of the sympathetic nervous system. 201Tl was used for landmarking. Planar anterior imaging was performed 15 min and 4 h after i.v. injection of 220 MBq 123I-MIBG and 37 MBq 201Tl. Image quantitation was based on the ratio of myocardial to mediastinal MIBG-uptake. Cardiac regions of interest were defined according to the 201Tl uptake. There was no evidence of sympathetic reinnervation in 8 patients 2-34 months after transplantation. Increased MIBG-uptake could be observed in the anterior basal region in 6 long-term cardiac transplants (37-69 months). One patient with a 59-month-old transplanted heart did not reinnervate. Increased MIBG-uptake in the anterior basal region indicating partial sympathetic reinnervation could be shown in 40% of the investigated patients with an average organ age of 51 months.
Thomas and Schmitz claim that they "deliver a proof for the effectiveness of humanistic methods" (p. 25) with their study. However, they did not or were not able to verify their claim due to several reasons: The authors did not say if and if so to what extent the treatments carried out within the framework of the TK-regulation were treatments using humanistic methods. The validity of the only criterium used by the authors, the average duration of the inability to work, must be questioned. The inferential statistical treatment of the data is insufficient; a non-parametrical evaluation is necessary. Especially missing are personal details concerning the treatment groups (age, sex, occupation, method, duration and frequency of therapy), which are indispensable for a differentiated interpretation. In addition there are numerous formal faults (wrong quotations, mistakes in tables, unclear terms etc.). In view of this criticism we come to the conclusion that the results are to a large degree worthless, at least until several of our objections have been refuted by further information and adequate inferential statistical methods. This study is especially unsuitable to prove a however defined "effectiveness of out-patient psychotherapies", therefore also not suitable to prove the effectiveness of those treatments conducted within the framework of the TK-regulation and especially not suitable to prove the superiority of humanistic methods in comparison with psychoanalytic methods and behavioural therapy.
In 31 patients with coronary artery disease (autonomic neuropathy, n = 11; diabetes without neuropathy, n = 10; silent myocardial ischemia without diabetes, n = 10) difference in somatic pain threshold and plethysmographically determined reactive hyperemia induced by forearm skeletal muscle ischemia was investigated. There was no difference in reactive hyperemia after passive maximum forearm ischemia in the three groups indicating identical vascular reactivity. After symptom-limited ischemic work however, reactive hyperemia was significantly higher in patients with silent myocardial ischemia as compared to diabetic patients. Exercise time was longer in patients with silent myocardial ischemia (153 +/- 51 s) as in patients with diabetic neuropathy (139 +/- 45 s) and diabetics without neuropathy (120 +/- 45 s). Pain as a cause of termination of symptom-limited ischemic forearm exercise occurred less frequently in patients with diabetic neuropathy (2/11) and patients with silent myocardial ischemia (3/10) as compared to patients with diabetes without neuropathy (9/10). In conclusion, patients with silent myocardial ischemia have a higher ischemic tolerance in the working forearm as compared to diabetic patients with and without neuropathy. There is a quantitative difference in ischemic tolerance between patients with silent myocardial ischemia and patients with diabetic neuropathy.
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Analytical gel filtration was used for the study of molecular size distribution of clinical dextran in serum and urine for the purpose of evaluations of changes in the human glomerular barrier function. The column was calibrated in terms of solute size using a simple and accurate technique recently described. Only one sample of a dextran possessing a broad molecular mass distribution was necessary for the calibration procedure and the calculations were performed using an ordinary spreadsheet. The accuracy of the calibration, as evaluated by protein samples, is better than 95%. The simplicity makes the method suitable for use in laboratories not normally specializing in analytical gel filtration. Calibration in terms of size is preferably done with respect to viscosity radius to obtain relevant information about the permeability of dextran into porous membranes.
To evaluate the course of cerebral tissue perfusion in patients with acute focal cerebral ischemia of the supratentorial compartment regional cerebral blood flow (rCBF) was measured on day 0, 7, 14, 21, and 28 in 132 patients using the 133 Xenon stationary inhalation technique. Ischemic events of the brainstem and hemorrhagic complications were excluded. The clinical status was evaluated using a modified Mathew score. In 34 patients no hemodilution, anti-edema therapy, or Ca(++)-antagonists were used but otherwise best medical therapy was applied. These patients represented the so called "natural course" of cerebral ischemia. In 30/34 patients on day 0 (within 16 hours after onset of symptoms) focal flow abnormalities were found in the involved side. In 9 of these 30 patients and in 1 of the remaining ischemia was observed in the contralateral side. rCBF above normal (relative luxury perfusion) despite pathologic neurologic findings was observed in 8/34 patients on day 3-7. Eight patients presented on day 3-7 with normal flow which later became ischemic again without evidence of another symptomatic episode. Correlation between severity of clinical findings and actual rCBF was low from day 3 to 7 but close on day 0. From day 14-21 hemispheric CBF correlated well with the total neurologic score but focal clinical findings had a lower correlation with focal flow as compared to day 0 and day 28. Contralateral ischemia was never found after day 14. In 5 other cases with "natural course" described above, a transitory decrease of rCBF below the initial ischemia level was found between day 3 and 14.(ABSTRACT TRUNCATED AT 250 WORDS)
Discrepant results have previously been reported concerning long-term left ventricular function in the human transplanted heart as assessed by radionuclide ventriculography. In this study, radionuclide ventriculograms were obtained at rest and during exercise in 19 patients < 6 months, 7-12 months, 13-24 months and > 24 months after transplantation. Ejection fraction decreased significantly from < 6 months to 13-24 months after transplantation (rest: 69.1% +/- 9.7% to 56.7% +/- 8.3%, P < 0.05; exercise: 70.4% +/- 11.3% to 59% +/- 8%, P < 0.05). Heart rate increased significantly during exercise after > 2 years (90.2 +/- 10.5 beats/min to 103.5 +/- 15 beats/min, P < 0.05) but not within 6 months after transplantation (98.5 +/- 12.8 beats/min to 99.07 +/- 15.8 beats/min). Left ventricular end-diastolic volume remained unchanged. Peak filling rate at rest decreased significantly from 4.2 +/- 0.96 edv/s < 6 months after transplantation to 3.3 +/- 0.66 edv/s (P < 0.05) 13-24 months and 3.3 +/- 0.64 edv/s (P < 0.05) > 24 months after cardiac transplantation. Exercise peak filing rate did not change significantly. It is concluded that radionuclide ventriculography demonstrates a decrease in systolic left ventricular function in the long-term course after cardiac transplantation. A significant increase in exercise peak heart rate may be due to autonomic reinnervation. Differences in the literature concerning left ventricular function may be due to different observation intervals following cardiac transplantation.
Iodine-123 metaiodobenzylguanidine (MIBG) is a noradrenaline analogue which can be used as a tracer to investigate the cardiac sympathetic nervous system. Regional ischaemia leads to noradrenaline depletion with functional denervation which can be demonstrated by reduced MIBG uptake. In order to evaluate the reversibility of ischaemia-associated damage to the sympathetic nervous system, neuronal scintigraphy with 123I-MIBG and myocardial rest and stress perfusion scintigraphy with technetium-99m sestamibi was performed in 16 patients with coronary artery disease before and 3-4 months after percutaneous transluminal coronary angioplasty (PTCA). Partial re-innervation occurred in five patients, the degree of stenosis of remaining lesions being estimated by repeat angiography to be below 40%. Unchanged MIBG defects could be confirmed in four patients with residual lesions of between 40% and 50%. Increased MIBG defects were shown in three patients with significant restenoses of more than 70%. In all patients the neuronal defects exceeded the ischaemia-induced or scar-associated perfusion defects. Three patients dropped out of this study: one for technical reasons, one due to emergency aortocoronary bypass surgery and one due to diabetic polyneuropathy. This investigation shows that the sympathetic nervous system is highly sensitive to ischaemia. Further studies need to be done to assess the conditions allowing re-innervation after PTCA.
In a traditional long-term study N-nitrosodibenzylamine (NDBzA) was proven to be noncarcinogenic, but recently the substance was found to produce genotoxic lesions in hepatocytes. Our own experiments have shown that relatively low single doses of NDBzA cause liver hypertrophy and additive proliferation of hepatocytes in rats. Both effects are known from well-documented promoters and non-genotoxic carcinogens, respectively, in rodents. Investigation of NDBzA in an initiation-promotion assay (IP assay) showed it to cause an increase in the number and size of preneoplastic liver cell foci. This occurred only after initiation with diethylnitrosamine, but not when 2-acetylaminofluorene was used. Another property of NDBzA is its sustained mitotic stimulation of extrafocal hepatocytes. This is inconsistent with their adaptive loss of susceptibility to mitogens in IP assays using other promoters of hepatocarcinogenesis. The following conclusions can be drawn. First, "differential inhibition" of the proliferation of extrafocal hepatocytes, in contrast to the selective mitostimulation of preneoplastic cells, is obviously no prerequisite for cancer development. Second, primary mitogenicity of a compound in short-term studies can be a useful indicator for tumorigenic potential. In the case of NDBzA the data available at present are still insufficient to classify it unequivocally in terms of genotoxic or nongenotoxic carcinogenicity.
Testing vasoreactivity with CO2 or Diamox is a common diagnostic procedure for the study of haemodynamics in stroke patients. CO2 reactivity (CO2R) was tested in 5 baboons six hours after permanent occlusion of the left middle cerebral artery (MCA) in order to attain new insights into interpretation of vasoreactivity tests. Using the microsphere method, cerebral blood flow (CBF) was determined in the various vascular territories as well as in the centre of the ischemia, the penumbra and the remaining MCA-tissue. CBF decreased significantly in the affected MCA in all animals and in addition in the contralateral cerebellum in one animal (p < 0.05). In addition, the left anterior cerebral artery (ACA) demonstrated a similar decrease. During hypercapnia CBF increased in all areas with the exception of the left, occluded MCA territory. Thus CO2 enhanced the difference between ischaemic and non-ischaemic tissue (i.e., tissue with diaschisis). Mean CO2 R was 3.37 ml/100 g/min/mmHg in the right MCA, 0.16 in the left. While the left ACA demonstrated a decreased perfusion during normocapnia in a similar range to the MCA territory, only CO2R was able to identify precisely the territory of the occluded vessel. CO2 R was zero or negative in the ischaemic core, close to zero in the penumbra and profoundly decreased in the remaining MCA tissue. The overall CO2 R of the MCA was almost zero, suggesting vasoparalysis in response to hypercapnia in the core and penumbra and exhausted CO2 R even in non-infarcted, non-penumbral tissue. One animal displayed a negative CO2 R equivalent to an intracerebral steal-phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased urinary albumin excretion, microalbuminuria, may be the first sign of early diabetic nephropathy. We examined glomeruli by morphometric methods in 17 patients with Type 1 (insulin-dependent) diabetes mellitus and microalbuminuria. The median age was 19 (range 18-29) years, duration of diabetes 12 (8-15) years, mean blood pressure 93 (87-115) mm Hg, glomerular filtration rate 132 (101-209) ml.min-1.1.73 m2 -2, albumin excretion rate (mean over 1 year) 32 (15-194) micrograms/min. Reference data were obtained from 11 healthy kidney donors. Mesangial volume estimates were obtained by serial sectioning in three total profiles in each of three glomeruli in diabetic patients. Basement membrane thickness and matrix volume fraction were estimated from one level per glomerulus. Two matrix parameters, matrix star volume and matrix thickness, were estimated. Interstitial volume fraction in cortex was measured by light microscopy. The morphological parameters were significantly increased in the diabetic group compared to the control group, basement membrane thickness (mean with 95% confidence intervals) was 595 nm (549-641 nm) vs 305 nm (287-325 nm), p = 0.0001; mesangial volume fraction 0.22 (0.21-0.23) vs 0.19 (0.18-0.21), p = 0.04, and matrix volume fraction 0.13 (0.12-0.13 vs 0.09 (0.08-0.10), p = 0.001. Also matrix star volume and thickness, interstitial volume fraction and mean capillary diameter were significantly increased. The intra-individual variation among glomeruli expressed as coefficient of variation was 7.4% vs 9% (basement membrane thickness) and 11.7% vs 25% (mesangial volume fraction) in the diabetic and the control group, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
To explore the integration of functional neuronal interactions in human higher cortical functions, we applied multivariate mathematical techniques to regional cerebral blood flow (rCBF) increases induced by mental activity. rCBF was measured using the intravenous xenon-133 clearance technique with 32 bihemispheric detectors in 84 normal volunteers at rest and during both a visuoperceptual accuracy task and a visuospatial problem solving task. Both paradigms activated rCBF in bilateral premotor, motor and postcentral regions. Bilateral prefrontal activation occurred during problem solving but not during the perceptual accuracy task. Partial correlations coefficients and factor analysis identified significant interactions between numerous cortex regions in both tasks. There were highly ordered and integrated patterns of functional interaction patterns between cortex areas subserving elementary subfunctions of complex behavior. Cortical interaction analysis by such techniques is a useful tool to describe the functional anatomy of large-scale neurocognitive networks in the intact human brain. Imaging functional interactions between active cortex areas are complementary to other experimental neurophysiologic methods to explore brain-behavior relationships in health and disease.
Mutants defective in phoB, the positive gene activator of the Escherichia coli pho regulon, exhibit aberrant behaviour on MacConkey indicator plates. They appear pale in the presence of a fermentable carbon source such as trehalose, maltose or glucose. The addition of at least 5 mM phosphate corrects this defect. Colonies of phoB+ strains turn red on MacConkey indicator plates and derepress the pho regulon when the cells are able to ferment the carbon source. In contrast, the inability to ferment the carbon source maintains the pho regulon in the repressed state.
We report on a young man who had absence of the septum and muscle in the corpora cavernosa. He had no tumescence or erection with either the nocturnal penile tumescence test or intracorporeal injection of a combination of vasoactive drugs. No other urological or extra-urological congenital defects were found. A malleable penile prosthesis was implanted.